A series of transformed rabbit cells were developed in this laboratory by co-culture of human T-cell lymphotrophic virus type I (HTLV-I)-infected rabbit or human leukemia-causing cells with rabbit peripheral blood mononuclear cells. These cell lines are being used to study viral gene expression and regulation of cellular processes as well as to study mechanisms of disease caused by HTLV-I, the human leukemia virus. The series of cell lines produced include cells with diverse in vitro and in vivo phenotypic characteristics, even though similar methods and virus were used to create them. All cell lines had HTLV-I provirus that was integrated at various sites in the genome. All cell lines produced p19 viral core protein and many exhibited productive-appearing virions in cytoplasmic vesicles or in extracellular spaces, when examined by transmission electron microscopy. All cell lines were capable of infecting and transforming cells when co-cultured with fresh rabbit peripheral blood mononuclear cells (PBMC). All rabbit cell lines lacked the CD4 receptor (CD4-), had T-cell antigen receptor (TCR) gene rearrangements and lacked immunoglobulin (Ig) lambda light chain gene rearrangement. Some cell lines utilize alpha/beta TCR while others use delta/gamma chains. Despite all these classical T-cell characteristics, cells exhibited a spectrum of phenotypic characteristics (within and) among cell lines, including different morphology, lysosomal contents, phagocytic capability and characteristics of in vitro growth. Some of the cell lines were lethal when inoculated into rabbits while others were not. A CD4- cell line expressing beta/delta TCR transcripts caused leukemia and lymphoma that resulted in the death of rabbits in a dose dependent manner. This disease is a model for the acutely lethal stage of adult T-cell leukemia/lymphoma (ATLL) occurring in some humans infected with HTLV-I. Characterization of this disease model is underway.